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21.
Osteoarthritis (OA) affects a large segment of the aging population and is a major cause of pain and disability. At present,
there is no specific treatment available to prevent or retard the cartilage destruction that occurs in OA. Recently, glucosamine
sulfate has received attention as a putative agent that may retard cartilage degradation in OA. The precise mechanism of action
of glucosamine is not known. We investigated the effect of glucosamine in an in vitro model of cartilage collagen degradation in which collagen degradation induced by activated chondrocytes is mediated by lipid
peroxidation reaction. Lipid peroxidation in chondrocytes was measured by conjugated diene formation. Protein oxidation and
aldehydic adduct formation were studied by immunoblot assays. Antioxidant effect of glucosamine was also tested on malondialdehyde
(thiobarbituric acid-reactive substances [TBARS]) formation on purified lipoprotein oxidation for comparison. Glucosamine
sulfate and glucosamine hydrochloride in millimolar (0.1 to 50) concentrations specifically and significantly inhibited collagen
degradation induced by calcium ionophore-activated chondrocytes. Glucosamine hydrochloride did not inhibit lipid peroxidation
reaction in either activated chondrocytes or in copper-induced oxidation of purified lipoproteins as measured by conjugated
diene formation. Glucosamine hydrochloride, in a dose-dependent manner, inhibited malondialdehyde (TBARS) formation by oxidized
lipoproteins. Moreover, we show that glucosamine hydrochloride prevents lipoprotein protein oxidation and inhibits malondialdehyde
adduct formation in chondrocyte cell matrix, suggesting that it inhibits advanced lipoxidation reactions. Together, the data
suggest that the mechanism of decreasing collagen degradation in this in vitro model system by glucosamine may be mediated by the inhibition of advanced lipoxidation reaction, preventing the oxidation
and loss of collagen matrix from labeled chondrocyte matrix. Further studies are needed to relate these in vitro findings to the retardation of cartilage degradation reported in OA trials investigating glucosamine. 相似文献
22.
Reactive oxygen species (ROS) are implicated in aging of cartilage and in the pathogenesis of osteoarthritis. However, the biological role of chondrocytes-derived ROS has not been elucidated. An in-vitro model was developed to study the role of chondrocyte-derived ROS in cartilage matrix degradation. The primary articular chondrocytes were cultured and the aggrecan matrix was radiolabeled with 35-sulfate. The labeled aggrecan matrix was washed to remove unincorporated label and chondrocytes were returned to serum free balanced salt solution. The cell-monolayer-matrix sensitivity to oxidative damage due to either hydrogen peroxide or glucose oxidase was established by monitoring the release of labeled aggrecan into the medium. Lipopolysaccharide (LPS) treatment of chondrocytemonolayer enhanced the release of labeled aggrecan. Catalase significantly prevented the release of labeled aggrecan in LPS-chondrocyte cultures, suggesting a role for chondrocyte-derived hydrogen peroxide in aggrecan degradation. Superoxide dismutase or boiled catalase had no such inhibitory effect. The effect of several antioxidants on LPS-chondrocyte-dependent aggrecan degradation was examined. Hydroxyl radical scavengers (mannitol and thiourea) significantly decreased aggrecan degradation. A spin trapping agent N-tert-butyl-phenylnitrone (but not its inactive analog tert-butyl-phenylcarbonate) significantly decreased aggrecan degradation. Butylated hydroxytoluene also inhibited aggrecan degradation, whereas the other lipophilic antioxidant tested, propyl gallate, had a marked dose-dependent inhibitory effect. These data indicate that general antioxidants, hydroxyl radical scavengers, antioxidant vitamins, iron chelating agents, lipophilic antioxidants, and spin trapping agents can influence chondrocyte-dependent aggrecan degradation. These studies support the role of a chondrocyte-dependent oxidative mechanism in aggrecan degradation and indicate that antioxidants can prevent matrix degradation and therefore may have a preventive or therapeutic value in arthritis. The enhancement of oxidative activity in chondrocytes and its damaging effect on matrix may be an important mechanism of matrix degradation in osteoarthritis. 相似文献
23.
Design and synthesis of substituted pyridine derivatives as HIF-1alpha prolyl hydroxylase inhibitors
Warshakoon NC Wu S Boyer A Kawamoto R Sheville J Bhatt RT Renock S Xu K Pokross M Zhou S Walter R Mekel M Evdokimov AG East S 《Bioorganic & medicinal chemistry letters》2006,16(21):5616-5620
Structure-guided de novo drug design led to the identification of a novel series of substituted pyridine derivatives as HIF-1alpha prolyl hydroxylase inhibitors. Pyridine carboxyamide derivatives bearing a substituted aryl group at the 5-position of the pyridine ring show appreciable activity, while constraining the side chain by placing a pyrazole carboxylic acid generated a potent lead series with consistent activity against EGLN-1. 相似文献
24.
Interleukin 1 production by human polymorphonuclear neutrophils 总被引:17,自引:0,他引:17
The purpose of this study was to determine whether human polymorphonuclear neutrophils (PMN), which share a common cell lineage with macrophages, could produce factors such as IL 1. Other properties which these two cell types share are their phagocytic nature and the common receptor and antigens on their cell surfaces. IL 1, in many of its physical, biochemical, and functional characteristics, is found to resemble endogenous pyrogen (EP). PMN have been cited as a possible cell source of EP, but there have also been reports in which the capacity of PMN to produce EP has been questioned. This study shows that normal human PMN can be stimulated by particulate agents such as zymosan and soluble agents such as phorbol myristic acetate to produce a factor(s) which induces proliferation of mouse thymocytes, i.e., PMN IL 1. This PMN IL 1 was released from PMN in a dose- and time-dependent fashion. PMN IL 1 was nondialyzable, was heat-labile, and was inactivated at pH below 5 and above 8. PMN IL 1 stimulated the proliferation of normal human synovial fibroblasts and caused release of a neutral protease (plasminogen activator) from synovial cells. The synovial and thymocyte-proliferating capacity of PMN IL 1 was not affected by the protease inhibitor aprotinin or by soybean trypsin inhibitor. Gel filtration studies estimate the m.w. of PMN IL 1 to be approximately 13,000 to 17,000. 相似文献
25.
26.
Sanjay Guleria A. K. Tiku Gurjinder Singh Apurva Koul Sahil Gupta Subhash Rana 《Journal of plant biochemistry and biotechnology.》2013,22(1):9-15
Antioxidant activities and phenolic contents of 26 species extracts from 20 botanical families grown in north-western Himalaya were investigated. Antioxidant activities were determined using DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging and ferric reducing antioxidant power (FRAP) assays. Total phenolic content (TPC) was determined using a Folin-Ciocalteu assay. Quantitative and qualitative analysis of phenolic compounds was also carried out by reverse phase high performance liquid chromatography (RP-HPLC) using diode array detector (DAD). Major phenolics determined using RP-HPLC in analyzed species were gallic acid, chlorogenic acid, p-hydroxy benzoic acid, caffeic acid, vanillic acid, syringic acid, p-coumaric acid and ferulic acid. Antiradical efficiency (1/EC50) determined using DPPH radical scavenging assay ranged from 0.13 to 5.46. FRAP values ranged from 8.66 to 380.9 μmol Fe(II)/g dw. Similarly, the total phenolic content in the analyzed species varied from 3.01 to 69.96 mg of gallic acid equivalents (GAE)/g dry weight. Gallic acid was found in the majority of the samples, being most abundant compound in Syzygium cumini bark (92.64 mg/100 g dw). Vanillic acid was the predominant phenolic compound in Picrorhiza kurroa root stolen (161.2 mg/100 g dry weight). The medicinal plants with highest antioxidant activities were Taxus baccata and Syzygium cumini. A significant positive correlation, R 2?=?0.9461 and R 2?=?0.9112 was observed between TPC determined using Folin-Ciocalteu method and antiradical efficiency and FRAP values respectively, indicating that phenolic compounds are the major contributor of antioxidant activity of these medicinal plants. 相似文献
27.
Kumar Varun Tiku Purnima Kaul 《International journal of peptide research and therapeutics》2021,27(2):977-985
International Journal of Peptide Research and Therapeutics - In the mammalian’s cells, a higher level of plasma cholesterol is a risk factor for cardiovascular disease. Human... 相似文献
28.
Glyoxalase system, particularly glyoxalase I (Gly I) plays an important role in regulation of cell division and is considered to be a metabolic indicator of cell proliferation. The glyoxalase system is likely to have a close link with cellular radiosensitivity. Therefore, we have examined the effect of adaptive and split-dose of -rays on the activity of Gly I in the liver and spleen of mice. For the adaptive response studies, mice pre-treated with a conditioning dose of 0.5 Gy were given a challenging dose of 4 Gy at varying time intervals. In the split-dose studies, a dose of 4 Gy was delivered into two equal fractions and spaced at different time intervals. The results show that pre-exposure to a conditioning dose or the fractionation of total dose decreased the specific activity of Gly I in the liver and spleen of mice. The decreased activity of Gly I was suggestive of protective action induced by the conditioning dose and fractionation of dose. The similar pattern of radiation response of Gly I probably supported the possibility of involvement of a common pathway in the radiation-induced adaptive and split-dose effect. From these observations a close link between the Gly I and the adaptive-response as well as the split-dose effect is speculated. Since, the glyoxalase system is vital for a variety of biological functions including cell division and repair, the present findings may have relevance in understanding the dose-fractionation as well as the biological defence induced by low doses of radiations. 相似文献
29.
Sanjay Guleria A. K. Tiku Sahil Gupta Gurjinder Singh Apurva Koul V. K. Razdan 《Journal of plant biochemistry and biotechnology.》2012,21(1):44-50
The essential oil obtained from fresh leaves of Eucalyptus teretecornis (family Myrtaceae) was analysed by gas chromatography/mass spectrometry (GC/MS). Twenty eight compounds were identified and ??-pinene (22.55%), ??-pinene (22.50%), 1,8-cineole (19.84%), limonene (5.62%), ??-fenchol (3.10%), ??-phellandrene (2.90%), ??-eudesmol (2.66%) and 4-(2-methylcyclohex-1-enyl)-but-2-enal (2.34%) were the main components. The antifungal activity of the essential oil was assayed against Alternaria alternata using bioautography. Two main bioactive components namely a1 (R f ?=?0.27) and a2 (R f ?=?0.33) were observed that produced inhibition zone of 4?mm and 8?mm in diameter respectively. The minimum inhibitory amount (MIA) of a1 and a2 against A. alternata was determined as 28???g and 10???g, respectively using bioautography assay. Components corresponding to a1 and a2 were determined as ??-fenchol (oxygenated monoterpene) and ??-eudesmol (oxygenated sesquiterpene) respectively using GC/MS analysis. The antioxidant activity of the essential oil and its bioactive fraction was evaluated by DPPH radical scavenging assay, ??-carotene/linoleic acid bleaching assay, reducing power assay and metal chelating assay. In addition fraction of the essential oil that showed antioxidant activity was analyzed using GC/MS and ??-fenchol, 4-terpineol and carvacrol were the main components. 相似文献
30.
Reactive oxygen species (ROS) are implicated in aging of cartilage and in the pathogenesis of osteoarthritis. However, the biological role of chondrocytes-derived ROS has not been elucidated. An in-vitro model was developed to study the role of chondrocyte-derived ROS in cartilage matrix degradation. The primary articular chondrocytes were cultured and the aggrecan matrix was radiolabeled with 35-sulfate. The labeled aggrecan matrix was washed to remove unincorporated label and chondrocytes were returned to serum free balanced salt solution. The cell-monolayer-matrix sensitivity to oxidative damage due to either hydrogen peroxide or glucose oxidase was established by monitoring the release of labeled aggrecan into the medium. Lipopolysaccharide (LPS) treatment of chondrocytemonolayer enhanced the release of labeled aggrecan. Catalase significantly prevented the release of labeled aggrecan in LPS-chondrocyte cultures, suggesting a role for chondrocyte-derived hydrogen peroxide in aggrecan degradation. Superoxide dismutase or boiled catalase had no such inhibitory effect. The effect of several antioxidants on LPS-chondrocyte-dependent aggrecan degradation was examined. Hydroxyl radical scavengers (mannitol and thiourea) significantly decreased aggrecan degradation. A spin trapping agent N-tert-butyl-phenylnitrone (but not its inactive analog tert-butyl-phenylcarbonate) significantly decreased aggrecan degradation. Butylated hydroxytoluene also inhibited aggrecan degradation, whereas the other lipophilic antioxidant tested, propyl gallate, had a marked dose-dependent inhibitory effect. These data indicate that general antioxidants, hydroxyl radical scavengers, antioxidant vitamins, iron chelating agents, lipophilic antioxidants, and spin trapping agents can influence chondrocyte-dependent aggrecan degradation. These studies support the role of a chondrocyte-dependent oxidative mechanism in aggrecan degradation and indicate that antioxidants can prevent matrix degradation and therefore may have a preventive or therapeutic value in arthritis. The enhancement of oxidative activity in chondrocytes and its damaging effect on matrix may be an important mechanism of matrix degradation in osteoarthritis. 相似文献